CN1244794A - Stabilized, dry pharmaceutical compositions for drug delivery and methods of preparing same - Google Patents
Stabilized, dry pharmaceutical compositions for drug delivery and methods of preparing same Download PDFInfo
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- CN1244794A CN1244794A CN98802084A CN98802084A CN1244794A CN 1244794 A CN1244794 A CN 1244794A CN 98802084 A CN98802084 A CN 98802084A CN 98802084 A CN98802084 A CN 98802084A CN 1244794 A CN1244794 A CN 1244794A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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Abstract
Dry, stabilized pharmaceutical spheres comprising a precisely measured amount of the pharmaceutical and a filler material that facilitates the immediate dissolution of the pharmaceutical upon contact with a solution are provided as well as methods for preparing same.
Description
The present invention relates to a kind of preparation method of novelty of stable dry drug preparation, this pharmaceutical preparation can be mixed with the liquid solution of accurate known concentration again.The present invention be more particularly directed to can be used for stablizing, preparing again then method with the drug solution of eye drop mode medication.
Drug solution must accurately be prepared, in order to avoid dosage is too much insufficient with treatment.In addition, medicine must be stable to the time, and to avoid two problems, one is that another is the issuable side effect of medicine catabolite because decomposition causes the effect reduction of effective ingredient.A well-known process that addresses this problem provides the medicine of dried forms, for example tablet or capsule, or the medicine of solid form, and for example medicated powder or lyophilization thing, they can mix with water or other appropriate solvent and preparation again.
Medicine is oral administration traditionally or passes through drug administration by injection.But, there are many medicines to be not easy via these method administrations.For example, a lot of medicine, particularly peptide classes, digestive enzyme that is existed in the gastrointestinal tract and/or acidity degraded therefore can not be oral.In addition, because goldbeater's skin is lower to the permeability of hydrophilic compounds, a lot of materials are difficult for being absorbed in gastrointestinal tract.Therefore, these medicines must pass through the parenteral route administration.
The another kind of method that discharges medicine is directly drug solution to be expelled in the blood flow, i.e. intravenous administration.But, this method generally can cause pain, also must be in administration under the aseptic condition, to prevent spreading of infectious disease, and must take preventive measures to avoid the problem that may produce by administration injection inadequately and to guarantee polluted needle and syringe head is carried out safe disposal.In addition, injection can cause unwanted side effect repeatedly, and for example necrosis, stimulation and local edema are that the control chronic disease is necessary and inject repeatedly usually, for example diabetes.
And, there are some diseases to be not suitable for utilizing injection to carry out the treatment of self-service mode, although this is the Therapeutic Method that needs most.For example, the hypoglycemia crisis is preferably treated with the method for intravenous, intramuscular or subcutaneous injection glucagon or intravenous injection glucose solution.Because motion function is impaired, the patient of hypoglycemic episodes is difficult for carrying out Heal Thyself by injection.But, treatment plays a decisive role again, because the hypoglycemia overlong time can cause irreversible stupor even death.In general, for the elevating blood concentration of glucose, patient's must take to take food method of confection, Fructus Vitis viniferae sugar-tablet or paste.This method is not ideal, and this is because containing sugar substance must arrive in the intestinal and absorb, and in the hypoglycemia crisis, the selection of time plays a decisive role.
In view of these reasons, new drug delivery system receives increasing concern, for example discharges by inhalation or the mode by the eye drop administration.United States Patent (USP) 5,182,258,5,278,142 and 5,283,236 have described a kind of like this system that carries out the release of medicine whole body via the eye approach.Since easy-to-use is a benefit of this drug delivery system, the method for compounding pharmaceutical solution is necessary simple as much as possible again with being used for stablizing medicine and quantitative high accuracy so.A method for optimizing that reaches this purpose provides the medicine of dried forms, and this medicine can accurately be prepared the solution that obtains known drug concentration again.A kind of like this requirement of dried forms is depended on using method and to the stable form that medicine is provided and the general requirement of accurate quantification.For example, when the single dose of drug that preparation is used immediately, the medicine of dried forms is dissolving fast.But, if prepared be to be used for the multiple dose medicine that discharges through stage considerable time, not all dosage all needs quick dissolving, has only first dose of needs administration immediately.Therefore, if the preparation method of pharmaceutical drying preparation can adapt to different release embodiments, will be significantly useful.
Further the practical difficulty that produces is, in preparation tablet and capsule, the process of mix dry powders can not be guaranteed uniformity.In addition, local impure situation may take place, make the impurity concentration of a tablet be higher than another tablet.And if there is not meticulous preventive measure, connecting dosage can not highly precisely control, and this is caused by the problem relevant with the mixing of solid constituent in preparation.Therefore, tablet is best suited for the medicine with extensive therapeutic domain.
Other provide the method for stablizing medicine to be seen in report.For example, United States Patent(USP) Nos. 5,624,597 and 5,413,732 have described the compositions that can be used for the analytical chemistry test.The disclosure of these patents relates to the formation of freeze dried bead, and this bead contains the reagent that is applicable to blood sample analysis.United States Patent(USP) Nos. 3,721,725 and 3,932,943 relate to the preparation method of freeze dried, and this method comprises that the activity that reagent is sprayed onto fluorocarbon coolants bathes in (moving bath), and the lyophilization gained freezes droplet then.U.S. Patent No. 4,848,094 discloses to be used for generating and is essentially the spheric method of freezing droplet and is used for removing improving one's methods of they from cryogenic liquid.U.S. Patent No. 4,655,047 has described the method that is used for freezing viscous drop, and this method is by viscous drop is splashed into the low temperature feedstock from lower height.U.S. Patent No. 4,678,812 and 4,762,857 have described and have contained the diagnosis tablet of trehalose as excipient and stabilizing agent.U.S. Patent No. 5,275,016 has described and a kind ofly can be used for utilizing cryogenic liquid to prepare the instrument of freezing droplet.U.S. Patent No. 4,982,577 have described the another kind of instrument that is used to prepare freezing beadlet.
Although these patent disclosures the preparation method of freezing droplet etc. of diagnostic reagent, still do not have known method can successfully prepare little, single dose, accurate measurement, dry or cryodesiccated solid globules or beadlet, wherein contain medicine, particularly peptide or polypeptide drugs.
The invention provides the preparation method of the solid pharmaceutical dosage of accurate measurement, this medicine is especially for the peptide or the polypeptide drugs of general disease, and they are uniformly on composition and weight, can also control its dissolution rate.
The present invention relates to composition and method of making the same, that said composition is used for being released in is stable, the medicine of the accurate measurement amount of dry matrices.Medicine in, the dry matrices stable at this can be immediately or is dissolved in the solution through the longer stage scheduled time, so that the drug solution that preparation is used for immediately and/or uses in the future.In a preferred embodiment, according to the disclosed method of common unsettled U.S. Patent application (attorney 260332000900), preparation is used for stable, the dry drug that discharge by ophthalmic administration, and the dry matrices that will contain this medicine joins to ocular drug and discharges in the device that carried out optimizing.
According to the present invention, medicine and filler are dissolved in a kind of solvent for example in the water, and filler is Polyethylene Glycol, inositol, polyvinylpyrrolidone, bovine serum albumin, dextrin, mannitol, trehalose, sodium carbonate, sodium bicarbonate, boric acid and salt thereof, glucose, sodium acetate, sodium phosphate or potassium phosphate, polyvinyl alcohol-polyvinyl acetate ester copolymer or the like for example.These filleies separately or be used in combination.Can add surfactant, for example Triton X-100
, sodium lauryl sulphate (sodium laurel sulfate), hexadecyltrimethylammonium chloride or the like.Also can add independent buffer components if necessary.If Pei Zhi solution will be stored certain hour again, also can comprise antiseptic in the preparation.The buffer components and the surfactant dissolves that are added with medicine and filler and when needing, preparation be solution uniformly basically.Term " evenly " should not be interpreted as hint may not exist colloid or micelle in liquid phase.Colloid, micelle and analog can be used as dispersion and exist, in the collochemistry field known, the mechanical behavior of this dispersion resembles true solution.Gained solution can outgas before dispersion alternatively, is separated into the droplet of accurate measurement then.The size of droplet is generally about 1.5 to about 20 microlitres.This process generally produces the dry beadlet of diameter about 1 to about 4mm, and this depends on the solids content of dispersion soln, its chemical composition and used this solid method of drying.
Lyophilization is the method for optimizing of the necessary rapidly-soluble beadlet of a kind of drying.Utilize a kind of precision pump that is generally the direct displacement type, by suitable nozzle pumping solution, to produce droplet.The internal diameter of nozzle is 0.010 to 0.050 inch, preferably is about 0.03 inch.Nozzle head generally is taper, and wall thickness is generally about 0.005 to about 0.020 inch, and this depends on the character of dispersed solution.The pump that is specially adapted to this purposes for example IVEK type AAA pump (N.Springfield, VT).The drip speed of solution when disperseing is that per second about 1 is to about 3.This drippage frequency does not have lower limit, and its upper limit is by being determined by the solidification rate of dispersed substance.
Dispersed droplet falls into liquid bath, makes droplet form solid globules.The mechanism that bead forms may be incompatibility or chemical reaction or their combination freezing, solvent.In a preferred embodiment, bead is by freezing formation, and freezingly realizes by making droplet fall into liquid nitrogen bath.Because after the freezing step is drying steps, is generally lyophilization, this method is mainly used to produce can dissolved immediately bead.What freeze-drying produced is low-density bead.In other words, solids has big void volume.
In another embodiment, bead is that incompatibility by solvent forms.Be slowly water-soluble when used filler but highly be dissolved in the miscible solvent of a kind of water that will produce the incompatibility of solvent, the miscible solvent of described water is for example ethanol, oxolane, acetone, dimethyl formamide or the like.In this embodiment, medicine, filler, buffer agent and surfactant are dissolved in the solvent.Droplet with the gained homogeneous solution is distributed in the big water-bath then.Water-bath can be cooled and/or contain salt, and for example the sodium chloride of high concentration (saline solution) solidifies beadlet with help.When droplet fell into water-bath, solvent mixed with water fast, made medicine in the inner rapid precipitation of bead.In this embodiment, the percentage ratio of filler must be higher (general＞20% solid) in the solution.Filter bead then or from water-bath, remove bead, and air-dry or oven dry.Needn't carry out lyophilization.
In another embodiment, utilize chemical reaction to form bead.In this embodiment, in filler solution, chemical reaction can take place in solution in subsequent reactions with medicine dissolution.For example, medicine is dissolved in high molecular multi-carboxylate's the concentrated solution, for example the sodium salt of styrene-maleic acid copolymer.Then this viscosity solution is distributed in the water-bath, comprises in this water-bath that a kind of pH fully is lower than the buffer components of effective pKa of styrene-maleic acid.In case solution mixes with water, proton transfer very rapidly then takes place, make the sodium salt of the water-soluble styrene-maleic acid of extreme enter styrene-maleic acid, the latter is can be very slowly dissolved.This reaction causes capturing the formation of solid globules of the acid of medicine.Equally, the gained bead must filter or remove from water-bath, and air-dry or oven dry.Needn't carry out lyophilization.
Be applicable to that medicine of the present invention includes but not limited to medicine and peptide and polypeptide drugs, for example glucagon, insulin, oxytocin, thyrotrophin-releasing hormone (TRH), leucine enkephalin, methionine-enkephalin, growth hormone, oxytocin, vassopressin, Schweine-Vasopressin, α-neoendorphin, β-neoendorphin, luteinizing hormone releasing hormone (LHRH), dynorphin A, dynorphin B, somatostatin, secretin, calcitonin, ACTH, growth hormone releasing hormone, Con A Concanavalin, ribonuclease, lysozyme, ribonuclease, β-lipotropin, γ-lipotropin or the like.
The following example is set forth the method that is used to prepare the drug release bead, and this drug release bead is used in the ocular drug delivery system.It only is for illustrational purpose that these embodiment are provided, in any case be not to limit the scope of the invention.Other aspects, advantage and modification in the scope of the invention will be conspicuous concerning those skilled in the art in the invention.
Here all patents of quoting, patent application and list of references integral body are incorporated this paper into as a reference.
Embodiment 1
Be used for the preparation of the quick dissolving bead of ocular drug release
Accurately weighing 9.806 gram CAPS buffer agents (3-hexamethylene amino-1-propane sulfonic acid) are dissolved in the 250mL deionized water with it, make buffer solution A.PH is transferred to 9.92.
Preparation filler solution B 1 promptly, contains 5.51 gram Polyethylene Glycol (MW2000) and adds 5.01 gram Polyethylene Glycol (MW3400) and add 6.006 gram Polyethylene Glycol (MW10,000) in 75mL buffer solution A.
Preparation filler solution B 2 promptly, contains 17.504 gram Polyethylene Glycol (MW10,000) in the 75mL solution A.
Preparation filler solution B 3 promptly, contains 15,008 gram Polyethylene Glycol (MW10,000) and adds 5.5012 gram Polyethylene Glycol (MW3400) in the 80mL solution A.
Preparation drug solution C promptly, contains the 15.6mg glucagon in the 7.5mL deionized water.
Prepare three kinds of dispersible preparationes.
In 7.5mL filler solution B 1, add 2.5mL drug solution C, preparation dispersible preparation F1.Dispersible preparation F1 contains 19.5% total solid.
In 7.5mL filler solution B 2, add 2.5mL drug solution C, preparation dispersible preparation F2.Dispersible preparation F2 contains 17.9% solid.
In 8mL filler solution B 3, add 2mL drug solution C, preparation dispersible preparation F3.Dispersible preparation F3 contains 23.5% solid.
These dispersible preparationes disperse with IVEK type AAA pump respectively.Drop volumes is transferred to 5 microlitres, and target weight is 5.3mg.Droplet is dispersed in the liquid nitrogen bath.Obtain following result:
Dispersible preparation F1 F2 F3
Discrete volume 5 μ L 5 μ L 5 μ L
Target weight 5.3mg 5mg 5mg
Average weight 5.323mg 5.299mg 5.284mg
Standard deviation 0.039mg 0.153mg 0.027mg
％CV 0.7 2.9 0.5
# sample 555
The beadlet 1,200 1,200 1300 that # produced
Then the refrigerated bead of gained is placed 12EL type Vertis freeze dryer (Gardener, NY) in and lyophilized overnight.Moisture residual in the bead is lower than 5%.Prepared whole beads are white, have uniform outward appearance and hard, slick surface.When placing water, all dissolvings fully in about 1 second of every type bead.
Embodiment 2
Preparation with quick dissolving bead that is used for ocular drug release of higher drug content
Accurately weighing 9.806 gram CAPS buffer agents are dissolved in the 250mL deionized water with it, make buffer solution A.PH is transferred to 9.92.
Preparation filler solution B 1 promptly, contains 5.51 gram Polyethylene Glycol (MW2000) and adds 5.01 gram Polyethylene Glycol (MW3400) and add 6.006 gram Polyethylene Glycol (MW10,000) in 75mL buffer solution A.
Preparation filler solution B 2 promptly, contains 17.504 gram Polyethylene Glycol (MW10,000) in 75mL buffer solution A.
Preparation filler solution B 3 promptly, contains 15.008 gram Polyethylene Glycol (MW10,000) and adds 5.5012 gram Polyethylene Glycol (MW3400) in 80mL buffer solution A.
Preparation drug solution C promptly, contains the 232mg glucagon in the 7.5mL deionized water.
Prepare three kinds of dispersible preparationes.
In 7.5mL filler solution B 1, add 2.5mL drug solution C, preparation dispersible preparation F1.This solution contains 20.2% total solid.
In 7.5mL filler solution B 2, add 2.5mL drug solution C, preparation dispersible preparation F2.This solution contains 18.6% solid.
In 8mL filler solution B 3, add 2mL drug solution C, preparation dispersible preparation F3.This solution contains 24.1% solid.
These dispersible preparationes disperse with IVEK type AAA pump respectively.Drop volumes is transferred to 5 microlitres, and target weight is 5.3mg.Droplet is dispersed in the liquid nitrogen bath.
Then the refrigerated bead of gained is placed 12EL type Vertis freeze dryer (Gardener, NY) in and lyophilized overnight.Moisture residual in the bead is lower than 5%.Prepared whole beads are white, have uniform outward appearance and hard, slick surface.When placing water, all dissolvings fully in about 1 second of every type bead.
Embodiment 3
The preparation that has higher drug content and replace the quick dissolving bead that is used for ocular drug release of solid matrix
Accurately weighing 9.806 gram CAPS buffer agents are dissolved in the 250mL deionized water with it, make buffer solution A.PH is transferred to 9.92.
Preparation filler solution B 1 promptly, contains 2 gram glucosans and adds 6.0 gram mannitols and add 1 gram trehalose in 75mL buffer solution A.
Preparation filler solution B 2 promptly, contains 17.5 gram Polyethylene Glycol (MW20,000) in 75mL buffer solution A.
Preparation filler solution B 3 promptly, contains 1 gram dextrin, 10 gram mannitols and 0.05 gram Triton X100 in 80mL buffer solution A.
Preparation drug solution C promptly, contains the 232mg glucagon in the 7.5mL deionized water.
Prepare three kinds of dispersible preparationes.
In 7.5mL filler solution B 1, add 2.5mL drug solution C, preparation dispersible preparation F1.Dispersible preparation F1 contains 12.7% total solid.
In 7.5mL filler solution B 2, add 2.5mL drug solution C, preparation dispersible preparation F2.Dispersible preparation F2 contains 16.1% solid.
In 8mL filler solution B 3, add 2mL drug solution C, preparation dispersible preparation F3.Dispersible preparation F3 contains 22.8% solid.
These dispersible preparationes disperse with IVEK type AAA pump respectively.Drop volumes is transferred to 5 microlitres, and target weight is 5.3mg.Droplet is dispersed in the liquid nitrogen bath.
With the refrigerated bead of gained place 12EL type Vertis freeze dryer (Gardener, NY) in and lyophilized overnight.Moisture residual in the bead is lower than 5%.Prepared whole beads are white, have uniform outward appearance and hard, slick surface.When placing water, all dissolvings fully in about 1 second of every type bead.
Embodiment 4
Utilize the solvent incompatibility to prepare slow dissolved bead
150mg sulfanilamide is dissolved in the 100mL oxolane and makes drug solution, also contain dissolved 20 gram polyethylene-polyvinyl alcohol copolymers in the described 100mL oxolane.Utilize 1500XL type or 2000XL type EDF pump (East Providence Road Island) that this solution is distributed in the 10 premium on currency bath that remains under 4 ℃, the size of droplet is 5 microlitres.In case run into water, oxolane promptly mixes with water, is settled out the insoluble polymer that carries faint water miscible medicine immediately.Blow with stream of warm air immediately with glomerular filtration, and to bead and to carry out drying in 10 minutes.
For having bigger water miscible medicine, before adding organic solution, water-bath uses medicine saturated in advance.Then with glomerular filtration, with the cold distilled water washing of small size, and as above method drying.
Embodiment 5
Utilize chemical reaction to prepare slow dissolved beadlet
The solution of preparation Urina Hominis (processed) medicine viadril, every 100mL distilled water contains the 10mg medicine.This is a kind of medicine of steroid type, and the dissolubility in low pH solution is very low.
With poly-(ethylene-maleic anhydride) copolymer of boiling water treating 25 grams,, make copolymer solution until the anhydride complete hydrolysis.In hot mixt, add a small amount of dense NaOH and quicken this process with neutralizing acid.When course of dissolution finished, gained pH was about 10.After the cooling, the 90mL copolymer solution is mixed with the 10mL drug solution.During 10 premium on currency that utilize EDF pump (on seeing) this solution to be distributed to the citrate buffer that contains 0.1M pH4 were bathed, the size of droplet was 5 microlitres.When droplet is run into solution in the water-bath, proton transfer promptly takes place once mixing, from solution, be settled out the ethylene-maleic acid that carries insoluble drugs.With the gained glomerular filtration, with cold deionized water or distilled water wash, and air-dry.During use, bead is prepared again with a kind of alkaline solution, for example the carbonate of pH 10 or borate buffer solution.Again preparation causes polymers swell, and medicine is dissolved in the alkaline medium.
Claims (26)
1. the preparation method of a medicine bead, this bead contain and are useful on where necessary the medicine of curee's administration, and this method comprises the following steps:
(a) medicine is dissolved in a kind of solvent, forms homogeneous solution;
(b) in the homogeneous solution of step a, add at least a filler;
(c) add a kind of buffer components in the solution that in step b, makes alternatively;
(d) add a kind of surfactant in the solution that in step b, makes alternatively;
(e) droplet with the accurate measurement of gained solution is distributed in a kind of liquid bath, forms solid globules; With
(f) bead that from liquid bath, forms among the separating step e.
2. the process of claim 1 wherein that this liquid bath contains a kind of cryogenic liquid, droplet is frozen thus.
3. the method for claim 2, this freezes the step of droplet further to comprise lyophilization, forms exsiccant medicine bead thus.
4. the process of claim 1 wherein that this liquid bath contains a kind of solvent that can be miscible with the solvent of step a, and wherein this medicine and filler only are sl. sol..
5. the method for claim 4 further comprises the step of the air-dry bead that has separated.
6. the process of claim 1 wherein that this liquid bath contains the chemical compound of at least a precipitable this filler.
7. the method for claim 6 further comprises the air-dry bead that has separated.
8. the process of claim 1 wherein that this medicine is a kind of peptide.
9. the process of claim 1 wherein that this medicine is a peptide species.
10. the method for claim 9, wherein this polypeptide is selected from the group of being made up of following: glucagon, insulin, oxytocin, thyrotrophin-releasing hormone (TRH), leucine enkephalin, methionine-enkephalin, growth hormone, oxytocin, vassopressin, Schweine-Vasopressin, α-neoendorphin, β-neoendorphin, luteinizing hormone releasing hormone (LHRH), dynorphin A, dynorphin B, somatostatin, secretin, calcitonin, ACTH, growth hormone releasing hormone, Con A Concanavalin, ribonuclease, lysozyme, ribonuclease, β-lipotropin and γ-lipotropin.
11. the method for claim 9, wherein this medicine is a glucagon.
12. the method for claim 9, wherein this medicine is an insulin.
13. the process of claim 1 wherein that this filler raw material is selected from the group of being made up of following: Polyethylene Glycol, inositol, polyvinylpyrrolidone, bovine serum albumin, dextrin, mannitol, trehalose, sodium carbonate, sodium bicarbonate, boric acid and salt thereof, glucose, sodium acetate, sodium phosphate or potassium phosphate and polyvinyl alcohol-polyvinyl acetate ester copolymer.
14. the process of claim 1 wherein that this surfactant is selected from the X-100 by Triton
, the group formed of sodium lauryl sulphate and hexadecyltrimethylammonium chloride.
15. the method for claim 1 further comprises the step that adds a kind of antiseptic in gained solution.
16. a compositions that contains according to the solid globules of claim 1 method preparation, this bead contains a kind of medicine and at least a filler raw material.
17. a compositions that contains drying, solid globules, this bead contain a kind of medicine and at least a filler raw material of accurate measurement amount, the amount of this filler raw material is enough to promote a kind of formation of substrate, and this substrate can direct solution enter this bead.
18. the compositions of claim 17 further contains a kind of surfactant.
19. the compositions of claim 17 further contains a kind of buffer components.
20. the compositions of claim 17, wherein this medicine is a kind of peptide.
21. the compositions of claim 17, wherein this medicine is a peptide species.
22. the compositions of claim 21, wherein this polypeptide is selected from the group of being made up of following: glucagon, insulin, oxytocin, thyrotrophin-releasing hormone (TRH), leucine enkephalin, methionine-enkephalin, growth hormone, oxytocin, vassopressin, Schweine-Vasopressin, α-neoendorphin, β-neoendorphin, luteinizing hormone releasing hormone (LHRH), dynorphin A, dynorphin B, somatostatin, secretin, calcitonin, ACTH, growth hormone releasing hormone, Con A Concanavalin, ribonuclease, lysozyme, ribonuclease, β-lipotropin and γ-lipotropin.
23. the compositions of claim 21, wherein this polypeptide is a glucagon.
24. the compositions of claim 21, wherein this polypeptide is an insulin.
25. the compositions of claim 17, wherein to carry out single dose administration immediately be enough to the amount of this medicine once dissolving in solution for this bead.
26. the compositions of claim 17, wherein the amount of this medicine is for being enough through sustained release administration after the stage scheduled time.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96566097A | 1997-11-06 | 1997-11-06 | |
| US08/965,660 | 1997-11-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1244794A true CN1244794A (en) | 2000-02-16 |
Family
ID=25510296
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98802084A Pending CN1244794A (en) | 1997-11-06 | 1998-11-04 | Stabilized, dry pharmaceutical compositions for drug delivery and methods of preparing same |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20040037889A1 (en) |
| EP (1) | EP0966271A1 (en) |
| JP (1) | JP2001507722A (en) |
| KR (1) | KR20000069889A (en) |
| CN (1) | CN1244794A (en) |
| AU (1) | AU1307399A (en) |
| WO (1) | WO1999024019A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2834212B1 (en) * | 2001-12-27 | 2004-07-09 | Besins Int Belgique | USE OF IMMEDIATE RELEASE POWDER IN PHARMACEUTICAL AND NUTRACEUTICAL COMPOSITIONS |
| WO2006106799A1 (en) * | 2005-03-31 | 2006-10-12 | Shionogi & Co., Ltd. | Microcapsule using polyvinyl alcohol copolymer |
| US9125807B2 (en) | 2007-07-09 | 2015-09-08 | Incept Llc | Adhesive hydrogels for ophthalmic drug delivery |
| JP5395794B2 (en) * | 2007-09-11 | 2014-01-22 | モンドバイオテック ラボラトリーズ アクチエンゲゼルシャフト | Use of galanin peptides as therapeutic agents |
| CA2750242C (en) | 2009-02-12 | 2018-05-22 | Incept, Llc | Drug delivery through hydrogel plugs |
| US9283305B2 (en) | 2009-07-09 | 2016-03-15 | Medtronic Vascular, Inc. | Hollow tubular drug eluting medical devices |
| US8678046B2 (en) | 2009-09-20 | 2014-03-25 | Medtronic Vascular, Inc. | Apparatus and methods for loading a drug eluting medical device |
| US8381774B2 (en) * | 2009-09-20 | 2013-02-26 | Medtronic Vascular, Inc. | Methods for loading a drug eluting medical device |
| US20110070358A1 (en) | 2009-09-20 | 2011-03-24 | Medtronic Vascular, Inc. | Method of forming hollow tubular drug eluting medical devices |
| US8828474B2 (en) | 2009-09-20 | 2014-09-09 | Medtronic Vascular, Inc. | Apparatus and methods for loading a drug eluting medical device |
| ES2362604B1 (en) | 2009-12-22 | 2012-06-28 | Bcn Peptides, S.A. | TYPICAL OPTIMAL FORMULATION OF PEPTIDES. |
| US9931296B2 (en) | 2010-04-03 | 2018-04-03 | Praful Doshi | Medical devices including medicaments and methods of making and using same |
| US10413506B2 (en) | 2010-04-03 | 2019-09-17 | Praful Doshi | Medical devices including medicaments and methods of making and using same including enhancing comfort, enhancing drug penetration, and treatment of myopia |
| US8632846B2 (en) | 2010-09-17 | 2014-01-21 | Medtronic Vascular, Inc. | Apparatus and methods for loading a drug eluting medical device |
| US8616040B2 (en) | 2010-09-17 | 2013-12-31 | Medtronic Vascular, Inc. | Method of forming a drug-eluting medical device |
| US8961501B2 (en) | 2010-09-17 | 2015-02-24 | Incept, Llc | Method for applying flowable hydrogels to a cornea |
| US8333801B2 (en) | 2010-09-17 | 2012-12-18 | Medtronic Vascular, Inc. | Method of Forming a Drug-Eluting Medical Device |
| ES2533601T3 (en) * | 2010-11-03 | 2015-04-13 | Arecor Limited | New composition comprising glucagon |
| US10226417B2 (en) | 2011-09-16 | 2019-03-12 | Peter Jarrett | Drug delivery systems and applications |
| AU2012347926B2 (en) | 2011-12-05 | 2018-03-15 | Incept, Llc | Medical organogel processes and compositions |
| US9486340B2 (en) | 2013-03-14 | 2016-11-08 | Medtronic Vascular, Inc. | Method for manufacturing a stent and stent manufactured thereby |
| CN107106641B (en) | 2014-10-31 | 2021-12-21 | 葛兰素史密斯克莱知识产权发展有限公司 | Powder formulation |
| WO2019239386A1 (en) | 2018-06-15 | 2019-12-19 | Ferring B.V. | Terlipressin compositions and uses thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5019400A (en) * | 1989-05-01 | 1991-05-28 | Enzytech, Inc. | Very low temperature casting of controlled release microspheres |
| US5578307A (en) * | 1992-01-17 | 1996-11-26 | Alfatec-Pharma Gmbh | Shaped articles containing plant extract(s), in particular pellets, and their pharmaceutical or cosmetic use |
| ES2108258T3 (en) * | 1992-01-17 | 1997-12-16 | Alfatec Pharma Gmbh | GRANULES CONTAINING PEPTIDIC DRUG SUBSTANCES AND THEIR PREPARATION AS WELL AS THEIR USE. |
| CA2129514A1 (en) * | 1992-03-12 | 1993-09-16 | M. Amin Khan | Controlled released acth containing microspheres |
| US5711968A (en) * | 1994-07-25 | 1998-01-27 | Alkermes Controlled Therapeutics, Inc. | Composition and method for the controlled release of metal cation-stabilized interferon |
| EP1013270A3 (en) * | 1992-12-02 | 2001-03-28 | Alkermes Controlled Therapeutics, Inc. | Controlled release growth hormone containing microspheres |
-
1998
- 1998-11-04 CN CN98802084A patent/CN1244794A/en active Pending
- 1998-11-04 AU AU13073/99A patent/AU1307399A/en not_active Abandoned
- 1998-11-04 EP EP98956584A patent/EP0966271A1/en not_active Withdrawn
- 1998-11-04 JP JP52685299A patent/JP2001507722A/en active Pending
- 1998-11-04 KR KR1019997006082A patent/KR20000069889A/en not_active Application Discontinuation
- 1998-11-04 WO PCT/US1998/023531 patent/WO1999024019A1/en not_active Application Discontinuation
-
2002
- 2002-11-20 US US10/301,765 patent/US20040037889A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999024019A1 (en) | 1999-05-20 |
| KR20000069889A (en) | 2000-11-25 |
| US20040037889A1 (en) | 2004-02-26 |
| AU1307399A (en) | 1999-05-31 |
| EP0966271A1 (en) | 1999-12-29 |
| JP2001507722A (en) | 2001-06-12 |
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